Management of refractory neonatal seizures

Figures & data

Table 1 Different seizure types, ictal electroencephalographic patterns, and clinical associations

Semiology	Ictal EEG correlate	Clinical association
Clonic (focal, segmentary, or bilateral)	Repetitive spikes	Various, frequent in neonatal stroke and other structural brain abnormalities
Myoclonic (erratic, fragmentary, or generalized)	May be prominent or completely absent	Metabolic or diffuse structural disorders
Tonic (resembles decerebrate rigidity or decorticate posture)	May be prominent or completely absent or rhythmic delta activity	Most often structural brain abnormalities, sometimes also metabolic disorders
Subtle (nystagmus, blinking, tonic eye deviations; pedaling, chewing, and sucking movements; apnea and/or vasomotor changes)	Sometimes flattening, may be normal, follow-up EEGs recommended	Various, frequent in hypoxic-ischemic encephalopathy

Notes: Data from Seshia et al³⁰ and Sivaswamy et al.³⁶ Table adapted from Plecko B. Neonatal seizures, including metabolic epileptic encephalopathies. In: Kennedy C, editor. Principles and Practice of Child Neurology in Infancy. London, UK: Mac Keith Press; 2012.⁶⁰ Copyright © John Wiley & Sons Ltd. Adapted with permisson of John Wiley & Sons Ltd.

Abbreviation: EEG, electroencephalography.

Table 2 Treatment options for neonatal seizures*

Drug	Loading dose	Maintenance	Remarks	References
First-line or second-line
Phenobarbitone	20–40 mg/kg IV over 20 minutes	5 mg/kg/day	Target level 40–60 μg/mL	^Citation26,Citation50,Citation76,Citation77
Phenytoin/phosphenytoin	20 mg/kg IV in 30 minutes	5 mg/kg/day	Target level 10–20 μg/mL	^Citation26,Citation50,Citation76,Citation77
Lorazepam	0.05–0.1 mg/kg IV in 5 minutes	8-hourly, if needed		^Citation26,Citation50,Citation53,Citation87,Citation88
Midazolam	0.05–0.2 mg/kg in 10 minutes	0.15–0.5 mg/kg/hour (maximum)	Slow increase	^Citation26,Citation50,Citation88
Clonazepam	0.1 mg/kg	0.01 mg/kg in 3–5 daily doses		^Citation50,Citation53,Citation90
Lidocaine (FT or >2.5 kg)	A 2 mg/kg IV in 10 minutes	7 mg/kg/hour for 4 hours, 3.5 mg/kg/hour for 12 hours, 1.75 mg/kg/hour for 12 hours then stop	Normothermia	^Citation78
	B 2 mg/kg IV in 10 minutes	7 mg/kg/hours for 3.5 hours, 3.5 mg/kg/hours for 12 hours, 1.75 mg/kg/hour for 12 hours then stop	Undergoing hypothermia treatment	^Citation78
Third line
Levetiracetam	25–50 mg/kg IV	5 mg/kg, may be increased		^Citation53,Citation92
Topiramate	5 mg/kg once daily	Up to 25 mg/kg/day via NGT		^Citation94
Lamotrigine	4.4 mg/kg single dose		Add-on	^Citation100
Valproate	10–25 mg/kg IV	10 mg/kg/day	(Oral)	^Citation97
Vigabatrin			Not sufficient data
Rarely used
Carbamazepine	5–20 mg/kg orally	5–8 mg/kg/dose, 2–3 doses/day		^Citation101
Paraldehyde	150 mg/kg/hour IV for 3 hours			^Citation102,Citation103
Felbamate			Probably unsuitable	^Citation106,Citation107
Bumetanide			Not sufficient data	^Citation104
Dexamethasone	0.6 mg/kg up to 2.8 mg/kg IV usually divided in four daily dosages	Given for 3–10 consecutive days		^Citation108,Citation109
Vitamins and minerals
Pyridoxal-5’-phosphate	100 mg (up to 500 mg) IV	30 mg/kg/day in 2–3 doses		^Citation26,Citation32,Citation56
Pyridoxal 5’-phosphate	30–50 mg/kg/day in 3–4 doses	3 consecutive days		^Citation26,Citation56,Citation69
Folinic acid	3–5 mg/kg/day in 2–3 doses	3 consecutive days		^Citation26, Citation56
Biotin	5–10 mg per day	Same daily		^Citation26

Notes:

* The authors confirm that the medication dosage schedules in the table are accurate, in accord with good medical practice and reflect a synthesis of the available medical literature at the time of publication. Because of ongoing research, changes in experience, information relating to drug therapy, and drug reaction reporting, changes in treatment dosages may occur. It is the responsibility of the practitioner to evaluate the appropriateness of the medications and dosages presented in the above table with due consideration for new developments in management strategies for neonatal seizures and emerging research.

Abbreviations: IV, intravenous; A, normothermia; B, hypothermia; NGT, nasogastric tube; FT, full term.

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